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表皮生长因子受体VIII(EGFRVIII)及表皮生长因子受体(EGFR)靶向嵌合抗原受体T细胞疗法治疗胶质母细胞瘤

EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma.

作者信息

Sterner Robert C, Sterner Rosalie M

机构信息

Department of Neurosurgery, Inova Fairfax Medical Campus, Fairfax, VA, United States.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.

出版信息

Front Oncol. 2024 Sep 19;14:1434495. doi: 10.3389/fonc.2024.1434495. eCollection 2024.

DOI:10.3389/fonc.2024.1434495
PMID:39364321
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11446898/
Abstract

Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, and radiation therapy, outcomes continue to be devastating for these patients with minimal improvements in survival. Chimeric antigen receptor T cell therapy is a revolutionary approach that is a new pillar in the treatment of cancer. CAR T cell therapy has produced remarkable results in hematological malignancies; however, multiple limitations currently prevent it from being a first-line therapy, especially for solid tumors. Epidermal growth factor receptor is classically amplified in glioblastoma, and a variant, EGFR variant III, is expressed on glioblastoma, making it an exciting potential target for CAR T cell therapy. Although preclinical has exciting potential, clinical data has been heterogeneous. In this review, we assess the state of field of EGFR-targeted CAR T cells.

摘要

胶质母细胞瘤是最常见的原发性脑肿瘤。尽管手术技术、化疗、免疫疗法和放射治疗都取得了重大进展,但这些患者的治疗结果仍然很糟糕,生存率几乎没有提高。嵌合抗原受体T细胞疗法是一种革命性的方法,是癌症治疗的新支柱。CAR T细胞疗法在血液系统恶性肿瘤中取得了显著成果;然而,目前存在的多种限制使其无法成为一线疗法,尤其是对于实体瘤。表皮生长因子受体在胶质母细胞瘤中经典性扩增,并且一种变体,即EGFR变体III,在胶质母细胞瘤中表达,这使其成为CAR T细胞疗法一个令人兴奋的潜在靶点。尽管临床前研究有令人兴奋的潜力,但临床数据却参差不齐。在本综述中,我们评估了靶向EGFR的CAR T细胞领域的现状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e04f/11446898/0266670dc1ab/fonc-14-1434495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e04f/11446898/0266670dc1ab/fonc-14-1434495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e04f/11446898/0266670dc1ab/fonc-14-1434495-g001.jpg

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Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.靶向复发性胶质母细胞瘤中表皮生长因子受体(EGFR)和白细胞介素13受体α2(IL13Rα2)的鞘内双特异性嵌合抗原受体(CAR)T细胞:1期试验中期结果
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Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.
嵌合抗原受体T细胞疗法治疗癌症后的神经精神表现:临床结局与管理策略的系统评价
J Immunother Cancer. 2024 Dec 22;12(12):e009174. doi: 10.1136/jitc-2024-009174.
脑室 CARv3-TEAM-E 细胞治疗复发性脑胶质瘤。
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Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.IL-13Rα2 靶向 CAR-T 细胞局部递送治疗复发性高级别脑胶质瘤:一项 1 期临床试验。
Nat Med. 2024 Apr;30(4):1001-1012. doi: 10.1038/s41591-024-02875-1. Epub 2024 Mar 7.
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Enhancing CAR-T cell metabolism to overcome hypoxic conditions in the brain tumor microenvironment.增强 CAR-T 细胞代谢以克服脑肿瘤微环境中的缺氧条件。
JCI Insight. 2024 Apr 8;9(7):e177141. doi: 10.1172/jci.insight.177141.
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Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.抗 EGFRvIII CAR T 细胞重复外周输注联合 pembrolizumab 治疗胶质母细胞瘤无效:一项 I 期试验。
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